Role of intra-accumbal cannabinoid CB1 receptors in the potentiation, acquisition and expression of morphine-induced conditioned place preference

Abstract

Recent studies demonstrate a functional interaction between opioid and endogenous cannabinoid system. These two systems possess similar pharmacological effects on drug addiction and reward. The present study was designed to investigate the role of intra-accumbal cannabinoid CB1 receptors in the acquisition and expression of morphine-induced conditioned place preference (CPP). Two-hundred forty eight adult male albino Wistar rats were used in these experiments. Using a 3-day schedule of conditioning, it was found that subcutaneous administration of morphine (0.2–10mg/kg) induced CPP at the doses of 5 and 10mg/kg. Solely intra-accumbal administration of WIN55,212-2 (1, 2 and 4mmol/0.5μl DMSO) as CB1 receptor agonist could induce CPP. Also, our results showed that ineffective dose of WIN55,212-2 (1mmol) when administered before the ineffective dose of morphine (2mg/kg) could induce the CPP and potentiate the rewarding effect of morphine. On the other hand, intra-accumbal injection of the cannabinoid CB1 receptor antagonist AM251 (90μmol/0.5μl DMSO) alone induced a significant conditioned place aversion. Moreover, intra-NAc injection of AM251 (45 and 90μmol/0.5μl DMSO) inhibited morphine-induced CPP. Interestingly, injection of WIN55,212-2 (1, 2 and 4mmol) or AM251 (15, 45 and 90μmol) into the NAc had no effect on the expression of morphine (5mg/kg)-induced CPP. These observations provide evidence that cannabinoid CB1 receptors in the NAc are involved in development of reward-related behaviors and they can potentiate the rewarding effects of morphine. It seems that these receptors can affect the reward modulatory system at the level of nucleus accumbens in rats.